Three-Component One-Pot Synthesis of Functionalized 1,2,3,6-Tetrahydropyrano[4,3-b]pyrroles

Abstract

T h r e e -C o m p o n e n t O n e -P o t S y n t h e s i s T e t r a h y d r o y r a n o [ 4 , 3 -b ] p y r r o l e sAbstract: The reactive 1:1 adduct, produced from the reaction between dialkyl acetylenedicarboxylates and 2,6-dimethylphenyl isocyanide, was trapped by methyl 2,4-dioxopentanoate to yield dialkyl 1-(2,6-dimethylphenyl)-4-methyl-2,3-dioxo-1,2,3,6-tetrahydropyrano[4,3-b]pyrrole-6,7-dicarboxylates in moderate yields.Isocyanides are compounds with an extraordinary functional group; its unusual valence structure and reactivity were discussed for over one and a half centuries. 1 Isocyanides are the only class of stable organic compounds with a formally divalent carbon. Owing to its reactivity the isocyanide group differs fundamentally from other functional groups.One of the classic themes in the chemistry of isocyanides is heterocyclic synthesis. 2,3 Among others, useful syntheses of oxazolines, 4 pyrroles, 5 imidazoles, 6 oxazoles, 7 and thiazoles 8 have been described. In continuation of our interest in the application of isocyanides in heterocyclic synthesis, 9,10 we now report the reaction between dialkyl acetylenedicarboxylates 1 and 2,6-dimethylphenyl isocyanide in the presence of methyl 2,4-dioxopentanoate. 11 This three-component one-pot synthesis leads to highly functionalized dialkyl 1-(2,6-dimethylphenyl)-4-methyl-2,3-dioxo-1,2,3,6-tetrahydropyrano[4,3-b]pyrrole-6,7-dicarboxylates 2a-c (Scheme 1).2,6-Dimethylphenyl isocyanide and acetylenic esters 1 in the presence of methyl 2,4-dioxopentanoate undergo a smooth reaction in CH 2 Cl 2 at room temperature to produce compounds 2a-c in moderate yields. A single-crystal X-ray diffraction study confirmed the identity of compound 2c. 12 An ORTEP diagram of 2c is shown in Figure 1.The mass spectra of these compounds are fairly similar and display molecular ion peaks. Any initial fragmentation involved the loss of the ester moieties. The 1 H NMR spectrum of compound 2a exhibited six single sharp lines, readily recognized as arising from methyl (d = 2.10, 2.12, and 2.67), methoxy (d = 3.06 and 3.79), and methine (d = 5.96) protons, together with a fairly complex multiplet in the aromatic region. The 13 C NMR spectrum of 2a showed twenty signals in agreement with the proposed 1,2,3,6-tetrahydropyrano[4,3-b]pyrrole structure. The 15 N NMR spectrum exhibited a signal at d = 155.8, downfield from external liquid ammonia, for the lactam nitrogen atom. The observed 15 N shift for 2a is in good agreement with the previously reported values for lactams. 13 The 1 H and 13 C NMR spectra of 2b and 2c are similar to those of 2a except for the ester groups, which exhibit characteristic signals with appropriate chemical shifts.Mechanistically, it is conceivable that the reaction involves the initial formation of a 1:1 zwitterionic intermediate 3 between 2,6-dimethylphenyl isocyanide and the acetylenic ester. Protonation of 3 by methyl 2,4-dioxopen- Scheme 1Downloaded by: University of Texas at San Antonio. Copyrighted material.

Highly efficient and green approach for the synthesis of spirooxindole derivatives in the presence of novel Brønsted acidic ionic liquids incorporated in UiO‐66 nanocages

“…We recently reported various synthetic methods for several biologically interesting products using nanocatalysts …”

Synthesis of New Tetrahydro‐1,5‐benzodiazepin‐3‐yl‐2‐phenylacetamides via Isocyanide‐Based Multicomponent Reactions

“…In recent years, isocyanide‐based multicomponent condensation reactions (IMCRs) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity, have attracted much attention because of the advantages that they offer to the field of combinatorial chemistry . Similarly, IMCRs have emerged as valuable tools for the preparation of structurally diverse chemical libraries of drug‐like heterocyclic compounds . In this context, benzodiazepine derivatives show interesting features that make them attractive for use in IMCRs .…”

ChemInform Abstract: Synthesis of New Tetrahydro‐1,5‐benzodiazepin‐3‐yl‐2‐phenylacetamides via Isocyanide‐Based Multicomponent Reactions.

“…In recent years, isocyanide-based multicomponent condensation reactions (IMCRs) by virtue of their synthetic potential, their inherent atom efficiency, convergent nature, ease of implementation, and the generation of molecular diversity, have attracted much attention because of the advantages that they offer to the field of combinatorial chemistry [10,11]. Similarly, IMCRs have emerged as valuable tools for the preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds [12][13][14][15][16]. In this context, benzodiazepine derivatives show interesting features that make them attractive for use in IMCRs [17][18][19][20][21][22][23].…”